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Developing safe therapies from human pluripotent stem cells

Nature Biotechnology volume 27, pages 606–613 (2009)Cite this article

Translation of human pluripotent stem cells into cell therapies will require the development of standardized tests for product consistency, stability, tumorigenicity, toxicity and immunogenicity.

The general strategy for many adult stem cell therapies and all pluripotent stem cell therapies is the scale-up of undifferentiated stem cells followed by differentiation to a specific cell type and delivery to the patient, where the cells may reside indefinitely. Some of the regulatory issues surrounding this strategy arise from the fundamental characteristics of living cells. Cells change over time both in vitro and in vivo, generally exist in a heterogeneous environment, integrate and migrate after transplantation and interact with host systems, such as the local milieu and the immune system. But cell products derived from pluripotent stem cells present additional issues that result from the two defining features of these cells: extensive replicative capacity and pluripotency. The ability of the cells to proliferate apparently indefinitely allows production of the very large quantities of cells needed for commercial cell products but also imposes a requirement to assess the stability of the cells over time in vitro. The pluripotency of the cells allows generation of a wide array of differentiated cell products but also entails the possibility of teratoma formation and the presence of unwanted cell types. This commentary addresses the regulatory issues specific to therapies with cells derived from pluripotent stem cells3,4. As the first clinical trials will use human embryonic stem cells (hESCs), we focus on this class of therapies; a penultimate section discusses several unique issues relevant to induced pluripotent stem cells (iPSCs).

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Figure 1: Schematic showing processing and manufacturing steps involved in developing a stem cell product.

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Author information

Authors and Affiliations

  1. Melissa K. Carpenter is at the Carpenter Group, San Diego, California, USA m_carpenter@mac.com,

    Melissa K Carpenter

  2. Joyce Frey-Vasconcells is at Pharmanet Consulting, Princeton, New Jersey, USA,

    Joyce Frey-Vasconcells

  3. Mahendra S. Rao is at Invitrogen Corp., Frederick, Maryland, USA.,

    Mahendra S Rao

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  2. Joyce Frey-Vasconcells
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  3. Mahendra S Rao
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Carpenter, M., Frey-Vasconcells, J. & Rao, M. Developing safe therapies from human pluripotent stem cells. Nat Biotechnol 27, 606–613 (2009). https://doi.org/10.1038/nbt0709-606

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